Background:Rheumatoid arthritisinflammatory joint disease which is chronic in nature. Since long various researches are carried out to find the remedy of this disease but still a lot of work needed to be done. Methods: This comparative study was performed from March to August 2013 at Postgraduate Medical Institute, Lahore.A total of thirty-two female Sprague-Dawley rats were randomly divided into four equal groups (n=8); group A was kept as healthy control, group Bwas kept as positive control, group C was treated with thymoquinone and group D was treated withmethotrexate. Arthritis developed within two weeks in group B, group C and group D after giving a single shot of pristane intradermally.Treatment was started on day 15. At day 30 (time of dissection) pawweightand histopathological sections of ankle joints of all the animals were taken.Results: The resultsshownsignificant rise inpaw weight and score of histopathological parametersin group B, group C and group D when compared withhealthy control rats. Thymoquinone and methotrexate treated groups shown reduction in paw weight and score ofhistopathological parameters when compared to positive control rats withp-value 0.001each. The difference between groups C and D was insignificant (p-value 0.062). Conclusion: Study results supported the anti-inflammatory and disease modifying activities of thymoquinone as it significantly reduces both paw weight and histological parameters of joint inflammation